DESCRIPTION:

Differentially expressed genes in male Sprague-Dawley rats (300-375 g or 250-300 g) following cocaine administration. Some animals expressed the H3.3 Q5A vector, which led to down-regulation of histone H3 glutamine 5 dopaminylation (H3Q5dop), which is involved in midbrain plasticity in response to cocaine. Gene expression was evaluated via RNA-seq. Data taken from Supplemental Table S4 (associated with Fig 2. E, G, and I). Values presented are p-values. Data available at GEO with accession number GSE124055.

LABEL:

H3.3 Q5A vs. H3.3 WT (Cocaine)

SCORE TYPE:

P-Value

DATE ADDED:

2021-06-25

DATE UPDATED:

2022-05-24

SPECIES:

AUTHORS:

Ashley E Lepack, Craig T Werner, Andrew F Stewart, Sasha L Fulton, Ping Zhong, Lorna A Farrelly, Alexander C W Smith, Aarthi Ramakrishnan, Yang Lyu, Ryan M Bastle, Jennifer A Martin, Swarup Mitra, Richard M O'Connor, Zi-Jun Wang, Henrik Molina, Gustavo Turecki, Li Shen, Zhen Yan, Erin S Calipari, David M Dietz, Paul J Kenny, Ian Maze

TITLE:

Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking.

JOURNAL:

Science (New York, N.Y.) 04 2020, Vol 368, pp. 197-201

ABSTRACT:

Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in the midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in the VTA. By reducing H3Q5dop in the VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated dopamine release in the nucleus accumbens, and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in the VTA. PUBMED: 32273471
Find other GeneSets from this publication